Most endogenous GFs are ________ that stimulate production of certain cell types.

glycoproteins

A ________ is a substance produced by endocrine glands, released in very low concentrations into the bl stream.

hormone

A hormone exerts regulatory effects on specific organs/tissues _______ the site of site of secretion. aka ________

distant from; endocrine

Some hormones are not proteins, like ________.

Steroids

__________ are synthetic molecules that bind to specific intracellular mRNA. They are made of about 13-25 nucleotides that are complementary to mRNA in a region of a coding sequence designed as a sense strand. By binding to mRNA, these stop translation.

Antisense oligonucleotides

__________ is used for the txm of CMV retinitis in persons w/ AIDS.

Vitravene (fomivirsen)

fomivirsen

Vitravene

Vitravene

fomivirsen

Vitravene is a(n) ______________.

antisense oligonucleotide (AS-ON)

__________ are RNA/DNA molecules that recognize specific proteins. They fold into a 3D structure and bind to proteins.

Aptamers

______ is an anti-VEGF inhibitor approved by the FDA for the txm of wet age-related macular degeneration (injected into eye)

Mucagen (pegaptanib Na injection)

pegaptanib sodium injection

Mucagen

Biologic drugs are homogeneous or heterogeneous mixtures?

heterogeneous

Biologics have a logP of > or < 0.5?

logP < 0.5

LogP of > 0.5 means high or moderate-low solubility

Moderate-low

Log P of < 0.5 means high or moderate-low solubility?

high

Biologics are distributed to any organ/tissue or are limited to plasma/extracellular fluid?

Limited to plasma/extracellular fluid

Are biologics routinely metabolized or catabolized to aa (peptides)?

catabolized to aa (peptides)

___________ is the movement of drug from the site of application into blood stream or target tissue.

Absorption

___________ is the effect of drug on non-target tissues or cells.

Toxicity

___________ is the transformation, detoxification, conjugation, or bioactivation (prodrugs) of drugs

Metabolism

___________ is the movement of drug from blood to target site of action; greatly affected by plasma protein binding

Distribution

Voraxaze converts methotrexate to its inactive metabolites ________ and ________.

DAMPA; glutamate

________ implies drug is administered by injection or infusion

Parenteral

For biologics, preferred routes of administration include _________ & ________.

parenteral; subcutaneous

What's a biologic (protein) that is administered by inhalation?

Exubera (inhaled insulin powder

_____ and _____ are examples of enzymes that don't end in '-ase' and catalyze the cleavage of peptides.

______ is indicated for adults and adolescents (12+) w/ moderate-severe persistent asthma who have a + skin test or in vitro reactivity to a perennial skin allergen and who s/s are inadequately controlled w/ inhaled corticosteroids.

Xolair (omalizumab)

Xolair (omalizumab) is administered ____________.

Subcutaneously

________ is an FDA-approved protein kinase inhibitor used in oncology.

Imatinib

_______ is another non '-ase' enzyme

Renin

Recently, patent expiration and loss of market exclusivity on several pharmaceuticals (biologics) stimulated a debate on the role of generic (____________) biologics.

Biosimilar; follow-on

___% of proteins are misfolded.

60

DNA = about ____ BP in humans and contains about _____ genes.

3 x 10^9; 25,000

Nuclear DNA contains about ___ Mb and ____ genes.

3,300; 25,000

Mitochondrial DNA contains about ___ kb and ___ genes.

16.6; 37

Out of nuclear DNA, __% is genes and __% is extragenic DNA.

25; 75

________ DNA are composed of repeats (tandem, clustered, or interspersed).

Extragenic

Out of nuclear genes, __% is coding DNA and __% is non-coding DNA (introns, UTR, fragments)

80% of those diagnosed w/ MELAS have a ________ mutation in dihydrouridine loop of tRNA.

3243 A --> G point

_________ explains the variation in severity of the disease among siblings.

Heteroplasmy

_________ is the presence of a mix of more than one type of an organelle genome (mtDNA) w/in a cell. It is frequent for mutations to affect only some copies of mtDNA, while the remaining ones are undaffected.

HDAC inhibitors (increase/decrease) acetylation of histones, thereby (increasing/decreasing) transcription of genes that have been silenced.

increase; increasing

HDAC inhibitors promote growth arrest by inducing the expression of __________ or _________ genes and are commonly used as anticancer drugs.

tumor-suppressor or pro-apoptotic

___ is the temperature it takes to unwind DNA.

90 C

_______ catalyzes dsDNA separation at origin.

Helicase

_______ stabilize ssDNA that has been separated

DNA binding proteins

_______ catalyzes the addition of short RNA primers to template strand.

DNA primase

_______ catalyzes the addition of new nucleotides to form new strands.

DNA polymerase

_______ catalyzes removal of RNA primer and inserts the correct bases (DNA pol has this kind of activity)

Exonuclease

_______ catalyzes the joining of Okazaki fragments and seals the sugar-phosphate backbone.

Ligase

Initiation--the replication origin is at a consensus sequence of 245 bps in the genome that is rich in ___________.

GATC sequence repeats

___________ is the enzyme that stays in front of the replication fork; introduces a nick in the DNA backbone allowing the rotation of one strand around the other, relieving torsional strain which would otherwise accumulate in front of the advancing fork.

Topoisomerase I

Topoisomerase inhibitors can be anti-cancer agents (FDA-approved) and include ______ and _______.

topotecan; ironotecan

At the heart of the replicating machinery is _______, which catalyzes synthesis of new DNA using old DNA as a template.

DNA pol

In prokaryotes, there are 3 major DNA pol known, but DNA pol __ is the principal replication enzyme in bacteria.

DNA pol III

DNA pol __ (eukaryotes) is responsible for the priming of replication of both strands.

alpha

DNA pol __ (euk) is responsible for the elongation of both strands.

delta

_________ is a measure of the avg no. of nucleotides added by a DNA pol enzyme per association/disassociation w/ the template.

Processivity

A ______ protein complex is required to keep DNA pol on the template and allow duplicaiton of long stretches of DNA

sliding clamp

In euk, the RNA primers are made at intervals of about ___ nucleotides on the lagging strand, and each primer is ___ nucleotides long.

200; 10

Primers are erased by _________ that recognized an RNA strand in an RNA/DNA helix and excise it; this leaves gaps that are filled by DNA pol III that can proofread.

exonuclease

DNA ligase catalyzes the formation of a _________ bond b/t the 3'-OH end of one fragment and the 5'-P end of the next, linking the sugar-phosphate backbones.

phosphodiester

A thermostable _____ polymerase is used in PCR.

Taq

What are the 3 steps of PCR (in order)?

Denature, anneal, extend

In PCR, annealing is also called___________.

hybridization

PCR primers are short, ssDNA mols that are about __ to __ bps long.

15-40 (primers are shorter in DNA replication)

______ quantifies PCR amplification as it occurs!

RT-qPCR (real time quantitative PCR)

After you amplify DNA, you can determine its sequence using the _______.

_________ is an antimicrobial approved for the txm of infections caused by MRSA and vancomycin-resistant E. fecalis.

Linezolid (Zyvox)

________ is a drug that inhibits bacterial protein synthesis by directly binding to residues w/in the 23S ribosomal RNA of the 560S large su of bact ribosomes (prevents peptide bond formation)

Linezolid (Zyvox)

________ is a drug that inhibits translation initiation; it binds to the 16S rRNA of bact ribosome, which prevents the release of the growing protein (pp chain). Have 3 rings that are connected by ether bonds.

Streptomycin

_______ is a drug that inhibits protein synthesis by blocking peptide transfer.

Chloramphenicol

_______ are a class of drugs that block A site on bact ribosome, that prevents binding of aminoacyl-tRNA

Tetracyclines

_____ protein structure is the sequence of a chain of aa.

Primary

_____ protein structure occurs when the sequence of aa are linked by H bonds.

Study of the organization and fxn of the complete genetic material of an organism

Genomics

For a given trait, the genes associated w/ the trait is _________.

The genotype

The observable expression of the genotype as a clinical, biochemical, or molecular trait is a _________.

phenotype

The tendency of certain disease phenotypes to appear at earlier ages and w/ increased severity in successive generations is ___________.

anticipation

_________ is a term used if individuals are related by blood prior to marriage or mating (e.g., first cousins)

Consanguinity

The proportion of people w/ a particular genetic change (a mutation in a specific gene) who exhibit s/s of a genetic disorder.

Penetrance

If people w/ a mutation don't develop features of the disorder, the condition is said to have ____________.

Reduced or incomplete penetrance

__________ is the extent to which a gene is expressed in one person. It can be graded as a %.

Expressivity

________ refers to whether the gene is expressed or not (how many people w/ the gen have the trait associated w/ the gene. ________ determines how much the trait affects/how many features of the trait appear in one person.

Penetrance; expressivity

The site on the chromosome at which a gene is located

Gene locus

Alternate forms of the same gene occupying the same locus on homologous chromosomes. These are called _________.

Alleles

A chromosome that isn't a sex chromosome (humans 1-22)

Autosome

(Dominant/Recessive) conditions usually involve structural proteins.

Dominant

(Dominant/Recessive) conditions usually involve enzyme deficiencies.

Recessive

_________ is a dominant disease in which the brain tissue gradually deteriorates in middle age. It is caused by the production of an inhibitor of brain cell metabolism.

huntington's disease

_________ is a dominant disease in which there is excessive CHO in the bl, leading to heart dz. It is caused by an abnormal form of CHO surface receptor.

Hypercholestrolemia

______ is a recessive disease in which mucus clogs the lungs, liver, and pancreas. It is caused by the failure of Cl ion transport mechanisms. (affects 1/2,500 Caucasians)